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. 2021 Mar 12:12:651288.
doi: 10.3389/fimmu.2021.651288. eCollection 2021.

Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?

Simone A Minnie  1 , Geoffrey R Hill  1   2
Affiliations

Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?

Simone A Minnie et al. Front Immunol. .

Abstract

The incidence of multiple myeloma (MM), a bone marrow (BM) resident hematological malignancy, is increasing globally. The disease has substantial morbidity and mortality and remains largely incurable. Clinical studies show that autologous stem cell transplantation (ASCT) remains efficacious in eligible patients, providing a progression free survival (PFS) benefit beyond novel therapies alone. Conventionally, improved PFS after ASCT is attributed to cytoreduction from myeloablative chemotherapy. However, ASCT results in immune effects beyond cytoreduction, including inflammation, lymphodepletion, T cell priming via immunogenic cell death, and disruption of the tumor BM microenvironment. In fact, a small subset of patients achieve very long-term control of disease post-ASCT, akin to that seen in the context of immune-mediated graft-vs.-myeloma effects after allogeneic SCT. These clinical observations coupled with recent definitive studies in mice demonstrating that progression after ASCT represents immune escape as a consequence of T cell exhaustion, highlight the potential for new immunotherapy maintenance strategies to prevent myeloma progression following consolidation with ASCT.

Keywords: T cells; autologous; immunotherapy; myeloma; stem cell transplantation.

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Conflict of interest statement

GH has received research funding from Compass Therapeutics, Roche, iTeos and Syndax. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. (2014) 124:344–53. 10.1182/blood-2014-02-514778 - DOI - PMC - PubMed
    1. Attal M, Lauwers-Cances V, Hulin C, Facon T, Caillot D, Escoffre M, et al. . Autologous transplantation for multiple myeloma in the era of new drugs: a phase III study of the intergroupe francophone du myelome (IFM/DFCI 2009 Trial). Blood. (2015) 126:391–1. 10.1182/blood.V126.23.391.391 - DOI
    1. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. . Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. (2010) 376:2075–85. 10.1016/S0140-6736(10)61424-9 - DOI - PubMed
    1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. . A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. (1996) 335:91–7. 10.1056/NEJM199607113350204 - DOI - PubMed
    1. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. . High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. (2003) 348:1875–83. 10.1056/NEJMoa022340 - DOI - PubMed

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